James Yurkovich, a Ph.D. student in the Bioinformatics and Systems Biology graduate program, is the lead author of a cover story in the Journal of Biological Chemistry.

Summary: In this study, we examined the temperature dependence of the human red blood cell metabolic network. The temperature dependence of biological functions had been previously studied at the levels of individual biochemical reactions and organism physiology (e.g., basal metabolic rates). Biology is inherently multi-scale, and there existed a gap between observing temperature dependence at the scale of an individual reaction and at the physiological level. We used a systems biology approach to define the temperature dependence of individual metabolite profiles, metabolic reaction fluxes, and the entire metabolic network. Our results provided an ex vivo characterization of temperature dependence, which is in contrast to previous studies of individual reactions that are determined through in vitro assays. Further, we provided a baseline characterization of a biochemical network given no transcriptional or translational regulation that can be used to explore the temperature dependence of metabolism. This paper was featured on the cover of the December 1, 2017 issue (Vol. 292, Num. 48); cover artwork by Rockford Penn, Technicity, LLC.

Rachel Marty has been awarded an NSF GROW fellowship to conduct research in cancer immunology at the University of Lausanne in Switzerland. The project entails computationally categorizing immune regions of the genome, such as HLA and KIR, and deciphering their roles in cancer. The NSF GROW (Graduate Resarch Opportunities Worldwide) Fellowship provides opportunities for students to engage in international research collaborations abroad. Rachel Marty received a B.S. in Computer Science with a specialization in Bioinformatics at UCSD and is currently in the Ph.D. program in Bioinformatics and Systems Biology at UCSD.

The National Science Foundation has awarded Graduate Research Fellowships to Ph.D. student Rachel Marty in the graduate Bioinformatics and Systems Biology program and to Max Shen in the undergraduate Bioinformatics program.

Olga Botvinnik, a Ph.D. student in the Bioinformatics and Systems Biology graduate program, has been awarded the 2014 John Hunter Fellowship. The focus of her Fellowship will be to create open source analysis software for the single-cell and biology communities, and to pioneer data, code sharing, and computational reproducibility within the single-cell and RNA biology communities.

The National Science Foundation has awarded Graduate Research Fellowships to Ph.D. students Leen Jamal and Jeffrey Yuan in the graduate Bioinformatics and Systems Biology program, and to students Robin Betz and Christopher Probert in the undergraduate Bioinformatics program.

One of the most basic and intensively studied processes in biology—one which has been detailed in biology textbooks for decades—has gained a new level of understanding, thanks to the application of simple math to a problem that scientists never before thought could benefit from mathematics.

The scientists who made the discovery, published in this week's advance online publication of Nature, found that the process bacteria use to quickly adapt to metabolize preferred energy sources such as glucose—a process called “catabolite repression”—is controlled not just by glucose, as had long been known and taught, but just as much by other essential nutrients, such as nitrogen and sulfur, available to bacteria in their growth medium.

“This is one of the most studied processes in molecular biology; it’s in every textbook,” says Terence Hwa, a professor of physics and biology at UC San Diego, who headed the team of scientists. “We showed that this process doesn’t work the way most people thought it did for the past several decades, and its purpose is different from what had generally been assumed.”

A biology and physics professor at UC San Diego has received a $1.15 million grant from the National Science Foundation to establish a series of annual “boot camps” that will educate San Diego-area high school and college students about an emerging field at the intersection of physics and biology called “quantitative biology.”

"Quantitative biology is more than adding numbers to what biologists already know,” says Suckjoon Jun, an assistant professor of physics and molecular biology, who received the five-year Faculty Early Career Development (CAREER) grant, awarded by the foundation to promising young scholar-researchers, and will work with a biology professor at San Diego State University to start the first of the boot camps next summer. “The power of the approach is to bring quantitative rigor from physical sciences to identify and solve important and interesting problems in biology.”

Two early-career scientists at UC San Diego are among 22 of the nation’s most enterprising researchers named Pew Scholars in the Biomedical Sciences by The Pew Charitable Trusts.

These scholars will each receive $240,000 over the next four years to pursue research projects without restriction that are focused on solving some of the nation’s most perplexing health problems—including diabetes, autism, Parkinson’s disease and cancer.

Andrew Huberman, an assistant professor of neurosciences, neurobiology and ophthalmology, and Suckjoon Jun, an assistant professor of physics and molecular biology, join a prestigious community of Nobel laureates, MacArthur Fellows, Albert Lasker Basic Medical Research Award winners and hundreds of other pioneers who earned Pew grants at the start of their careers.

One of the newest faculty members at UC San Diego—Suckjoon Jun, an assistant professor of physics and molecular biology—has won a $1.6 million award from the Paul G. Allen Family Foundation. This is the first award given to a UC San Diego recipient from the foundation, which was established by the co-founder of Microsoft to support high-risk, high-reward ideas in science. Jun’s effort is one of five awards announced by the foundation last week to projects “that aim to unlock key questions in the areas of cellular decision making and modeling dynamic biological systems.”

Livermore, CA - February 14, 2013 - The Fannie and John Hertz Foundation announces its finalists for the 2013-2014 Hertz Fellowship. From among more than 700 applicants, 50 are chosen as finalists to receive the Hertz Fellowship. The new Fellows will be announced by April 1st. Considered to be the Nation’s most generous support for graduate education in the applied physical, biological and engineering sciences, the Hertz Fellowship has been awarded to over 1100 individuals. Valued at more than a quarter million dollars per student, this support lasts for up to five years.

Abstract: Genetic adaptation to external stimuli occurs through the combined action of mutation and selection. A central problem in genetics is to identify loci responsive to specific selective constraints. Over the last two decades, many tests have been proposed to identify genomic signatures of natural selection. However, the power of these tests changes unpredictably from one dataset to another, with no single dominant method. We build upon recent work that connects many of these tests in a common framework, by describing how positive selection strongly impacts the observed site frequency spectrum (SFS). Many of the proposed tests quantify the skew in SFS to predict selection. Here, we show that the skew depends on many parameters, including the selection coefficient, and time since selection. Moreover, for each of the different regimes of positive selection, informative features of the scaled SFS can be learned from simulated data and applied to population-scale variation data. Using support vector machines, we develop a test that is effective over all selection regimes. On simulated data, our test outperforms existing ones over the entire parameter space. We apply our test to variation data from Drosophila melanogaster populations adapted to hypoxia, and identify loci that were missed by previous approaches, strengthening the role of the Notch pathway in hypoxia tolerance. We further apply our test to human variation data, and identify several regions that are in agreement with earlier studies, as well as many novel regions.

The Program and everyone who knew him was saddened today by the news of the passing of Professor Virgil Woods, an innovator of mass spectrometry and structural bioinformatics, and an engaging colleague, advisor and committee member to several of the Program students.

A study led by researchers at the UC San Diego Stem Cell Research program and funded by the California Institute for Regenerative Medicine (CIRM) looks at an important RNA binding protein called LIN28, which is implicated in pluripotency and reprogramming as well as in cancer and other diseases. According to the researchers, their study – published in the September 6 online issue of Molecular Cell – will change how scientists view this protein and its impact on human disease.

An international team of researchers led by computer scientist Pavel Pevzner, from the University of California, San Diego, have developed a new algorithm to sequence organisms’ genomes from a single cell faster and more accurately. The new algorithm, called SPAdes, can be used to sequence bacteria that can’t be submitted to standard cloning techniques—what researchers refer to as the dark matter of life, from pathogens found in hospitals, to bacteria living deep in ocean or in the human gut. Ultimately, the researchers hope to apply this algorithm to cancer cells to monitor early stages of the disease when normal cells first turn into malignant ones. Pevzner and colleagues published their findings in the May issue of the Journal of Computational Biology.

Bioengineers at the University of California, San Diego have developed a method of modeling, simultaneously, an organism’s metabolism and its underlying gene expression. In the emerging field of systems biology, scientists model cellular behavior in order to understand how processes such as metabolism and gene expression relate to one another and bring about certain characteristics in the larger organism.

In addition to serving as a platform for investigating fundamental biological questions, this technology enables far more detailed calculations of the total cost of synthesizing many different chemicals, including biofuels. Their method accounts, in molecular detail, for the material and energy required to keep a cell growing, the research team reported in the journal Nature Communications.

“With this new method, it is now possible to perform computer simulations of systems-level molecular biology to formulate questions about fundamental life processes, the cellular impacts of genetic manipulation or to quantitatively analyze gene expression data,” said Joshua Lerman, a Ph.D. candidate in Bernhard Palsson’s Systems Biology Research Group.

Using a new assay method to study tumor cells, researchers at the University of California, San Diego School of Medicine and UC San Diego Moores Cancer Center have found evidence of clonal evolution in chronic lymphocytic leukemia (CLL). The assay method distinguishes features of leukemia cells that indicate whether the disease will be aggressive or slow-moving, a key factor in when and how patients are treated.

Biologists at UC San Diego have discovered a chemical that offers a completely new and promising direction for the development of drugs to treat metabolic disorders such as type 2 diabetes—a major public health concern in the United States due to the current obesity epidemic.

Their discovery, detailed in a paper published July 13 in an advance online issue of the journal Science, initially came as a surprise because the chemical they isolated does not directly control glucose production in the liver, but instead affects the activity of a key protein that regulates the internal mechanisms of our daily night and day activities, which scientists call our circadian rhythm or biological clock.

The team was headed by Prof. Steve Kay, dean of the Division of Biological Sciences and a faculty member of the Bioinformatics and Systems Biology program.

Hemimegalencephaly is a rare but dramatic condition in which the brain grows asymmetrically, with one hemisphere becoming massively enlarged. Though frequently diagnosed in children with severe epilepsy, the cause of hemimegalencephaly is unknown and current treatment is radical: surgical removal of some or all of the diseased half of the brain.

In a paper published in the June 24, 2012 online issue of Nature Genetics, a team of doctors and scientists, led by researchers at the University of California, San Diego School of Medicine and the Howard Hughes Medical Institute, say de novo somatic mutations in a trio of genes that help regulate cell size and proliferation are likely culprits for causing hemimegalencephaly, though perhaps not the only ones.

Strains of bacteria able to resist multiple antibiotics pose a growing threat to public health, yet the means by which resistance quickly emerges aren’t well understood. Scientists led by physics professor Terence Hwa at the University of California, San Diego, thought that the variety of environments in which bacteria encounter antibiotic drugs could play an important role. They have developed a mathematical model, published in the June 18 early online edition of the Proceedings of the National Academy of Sciences, that demonstrates how that would work.

In the June 13 issue of Science Translational Medicine, an international team led by researchers from the University of California, San Diego School of Medicine reports that the new technology of exome sequencing is not only a promising method for identifying disease-causing genes, but may also improve diagnoses and guide individual patient care.

In exome sequencing, researchers selectively and simultaneously target and map all of the portions of the genome where exons reside. Exons are short, critical sequences of DNA in genes that are translated into proteins – the biological workhorses involved in virtually every cellular function, plus various structural or mechanical duties.

The researchers, headed by principal investigator Joseph G. Gleeson, MD, professor of neurosciences and pediatrics at UC San Diego and Rady Children’s Hospital-San Diego, sequenced the exomes of 118 patients who had been diagnosed with specific neurodevelopmental diseases. In each of the cases, all known genetic causes of their disease had been previously excluded.

Five scientists from the University of California, San Diego and its School of Medicine have been awarded almost $12 million in new grants from the California Institute for Regenerative Medicine (CIRM) to conduct stem cell-based research into regenerating spinal cord injuries, repairing gene mutations that cause amyotrophic lateral sclerosis and finding new drugs to treat heart failure and Alzheimer’s disease. Awardees include two faculty members in the Bioinformatics and Systems Biology Program: Lawrence Goldstein, who is studying Alzheimer's Disease, and Gene Yeo, who is studying Lou Gehrig's disease.

The National Academy of Sciences today elected three professors at the University of California, San Diego to membership in the prestigious National Academy of Sciences, one of the highest honors bestowed on U.S. scientists and engineers. Roberto Malinow, Ruth Williams and William Young were among the 84 new members and 21 foreign associates elected to the academy today “in recognition of their distinguished and continuing achievements in original research.” Ruth Williams, a professor in the Department of Mathematics, is a member of the Graduate Program in Bioinformatics and Systems Biology.

Researchers at the University of California, San Diego, the Medical University of South Carolina, the University of Cincinnati, and American Life Science Pharmaceuticals of San Diego have validated the protease cathepsin B (CatB) as a target for improving memory deficits and reducing the pathology of Alzheimer’s disease (AD) in an animal model representative of most AD patients. The study has been published in the online edition of the Journal of Alzheimer’s Disease.

According to investigator Vivian Y. H. Hook, PhD, professor of the UCSD Skaggs School of Pharmacy and Pharmaceutical Sciences and professor of neurosciences, pharmacology and medicine at the UCSD School of Medicine, and professor in the Bioinformatics and Systems Biology Graduate Program, the study is important because it could lead to new therapeutics that improve the memory deficits of AD.

Writing in the February 17, 2012 issue of the journal Cell, researchers at the Ludwig Institute for Cancer Research, the University of California, San Diego School of Medicine and the Toronto Western Research Institute peel away some of the enduring mystery of how zygotes or fertilized eggs determine which copies of parental genes will be used or ignored.

In the Cell paper, a team of scientists, led by Bing Ren, PhD, head of the Laboratory of Gene Regulation at the Ludwig Institute for Cancer Research at UC San Diego, describe in greater detail how differential DNA methylation in the two parental genomes set the stage for selective expression of imprinted genes in the mouse. Differential DNA methylation is essential to normal development in humans and other higher organisms. It involves the addition of hydrocarbon compounds called methyls to cytosine, one of the four bases or building blocks of DNA. Such addition alters the expression of different genes, boosting or suppressing them to help direct embryonic growth and development.

Led by researchers at the University of California, San Diego School of Medicine, scientists have, for the first time, created stem cell-derived, in vitro models of sporadic and hereditary Alzheimer’s disease (AD), using induced pluripotent stem cells from patients with the much-dreaded neurodegenerative disorder.

“Creating highly purified and functional human Alzheimer’s neurons in a dish – this has never been done before,” said senior study author Lawrence Goldstein, PhD, professor in the Department of Cellular and Molecular Medicine, Howard Hughes Medical Institute Investigator and director of the UC San Diego Stem Cell Program. “It’s a first step. These aren’t perfect models. They’re proof of concept. But now we know how to make them. It requires extraordinary care and diligence, really rigorous quality controls to induce consistent behavior, but we can do it.”

The feat, published in the January 25 online edition of the journal Nature, represents a new and much-needed method for studying the causes of AD, a progressive dementia that afflicts approximately 5.4 million Americans. More importantly, the living cells provide an unprecedented tool for developing and testing drugs to treat the disorder. Coauthors include Bioinformatics faculty members Lawrence Goldstein and Kun Zhang.

In eukaryotes – the group of organisms that include humans – a key to survival is the ability of certain proteins to quickly and accurately repair genetic errors that occur when DNA is replicated to make new cells.

Using Saccharomyces cerevisiae, or baker’s yeast, as their model organism, the researchers, led by Richard D. Kolodner, PhD, Ludwig Institute investigator and UCSD professor of medicine and cellular and molecular medicine, discovered that newly replicated DNA produces a temporary signal for 10 to 15 minutes after replication which helps identify it as new – and thus a potential subject for MMR.

In an example of life imitating art, biologists and bioengineers at UC San Diego have created a living neon sign composed of millions of bacterial cells that periodically fluoresce in unison like blinking light bulbs.

Their achievement, detailed in this week’s advance online issue of the journal Nature, involved attaching a fluorescent protein to the biological clocks of the bacteria, synchronizing the clocks of the thousands of bacteria within a colony, then synchronizing thousands of the blinking bacterial colonies to glow on and off in unison.

Coauthors include two members of the Bioionformatics and Systems Biology program: Ph.D. candidate Phillip Samayoa and Prof. Jeff Hasty.

Cells develop and thrive by turning genes on and off as needed in a precise pattern, a process known as regulated gene transcription. In a paper published in the November 9 issue of the journal Cell, researchers at the University of California, San Diego School of Medicine say this process is even more complex than previously thought, with regulated genes actually relocated to other, more conducive places in the cell nucleus.

Researchers have developed a new method to sequence and analyze the dark matter of life—the genomes of thousands of bacteria species previously beyond scientists’ reach, from microorganisms that produce antibiotics and biofuels to microbes living in the human body.

Scientists from UC San Diego, the J. Craig Venter Institute and Illumina Inc., published their findings in the Sept. 18 online issue of the journal Nature Biotechnology. The breakthrough will enable researchers to assemble virtually complete genomes from DNA extracted from a single bacterial cell. By contrast, traditional sequencing methods require at least a billion identical cells, grown in cultures in the lab. The study opens the door to the sequencing of bacteria that cannot be cultured—the lion’s share of bacterial species living on the planet.

Even the merest of microbes must be able to talk, to be able to interact with its environment and with others to not just survive, but to thrive. This cellular chatter comes in the form of signaling molecules and exchanged metabolites (molecules involved in the process of metabolism or living) that can have effects far larger than the organism itself. Humans, for example, rely upon thousands of products derived from microbially produced molecules, everything from antibiotics and food supplements to ingredients used in toothpaste and paint.

Remarkably, most of what’s known about how microbes communicate with each other is the result of indirect observation and measurements. There has been no general or informative technique for observing the manifold metabolic exchange and signaling interactions between microbes, their hosts and environments. Until now. In a paper published in the May 5 online issue of the journal Angewandte Chemie, researchers at UC San Diego and Scripps Institution of Oceanography report using a new form of imaging mass spectrometry to dramatically visualize multiplex microbial interactions.

UC San Diego scientists garnered 8 of the total 27 of Basic Biology III awards announced today by the Independent Citizens' Oversight Committee (ICOC) of the California Institute for Regenerative Medicine, the state agency created by California voters to pursue the promise of stem cells in science and medicine. “Basic science has been our strength at UC San Diego because we have dedicated time and energy to developing our expertise in stem cells,” said Larry Goldstein, PhD, director of the UC San Diego Stem Cell Program. “Through our excellence in scientific research fundamentals, UCSD stem cell researchers are creating the basis for future advances in this exciting field.”

The National Academy of Sciences today elected three professors at the University of California, San Diego to membership in the National Academy of Sciences, one of the highest honors bestowed on U.S. scientists and engineers. Herbert Levine, J. Andrew McCammon and David T. Sandwell were among the 72 new members and 18 foreign associates elected to the academy today "in recognition of their distinguished and continuing achievements in original research."

The National Academy of Sciences today elected three professors at the University of California, San Diego to membership in the National Academy of Sciences, one of the highest honors bestowed on U.S. scientists and engineers.

Andrew McCammon, the Joseph E. Mayer Chair of Theoretical Chemistry, Howard Hughes Medical Institute investigator and distinguished professor of chemistry and biochemistry, and pharmacology, and faculty in the Bioinformatics and Systems Biology Graduate Program, has invented theoretical methods for accurately predicting and interpreting how molecules interact with one another, methods that play a growing role in the design of new drugs and other materials.

The Alfred P. Sloan Foundation has awarded research fellowships to seven young faculty members at the University of California, San Diego, the largest group from a single institution to be recognized this year. Recipients include Bioinformatics & Systems Biology faculty members Leor Weinberger and Gene Yeo.

The California Institute for Regenerative Medicine (CIRM) has awarded three grants totaling nearly $5.8 million to researchers at the University of California, San Diego for development of innovative technologies designed to advance translational stem cell research. The grants are part of $32 million in Tools and Technology Awards II awarded to 19 projects at 10 California institutions that were announced by CIRM today. The grants were awarded to Lawrence Goldstein, Karl Willert, and Shu Chien.

Eight professors at the University of California, San Diego have been named new Fellows of the American Association for the Advancement of Science (AAAS), the world’s largest general scientific society. Philip E. Bourne, Xiang-Dong Fu, Kun-Liang Guan, Yishi Jin, Peter J. Novick, Bernhard Palsson and Kang Zhang were among 503 AAAS members selected by colleagues in their disciplines to be honored this year for “efforts toward advancing science applications that are deemed scientifically or socially distinguished.”

Researchers at the University of California, San Diego School of Medicine, led by Lucila Ohno-Machado, MD, PhD, chief of the Division of Biomedical Informatics in the Department of Medicine, have received two federal grants totaling more than $25 million to develop new ways to gather, analyze, use and share vast, ever-increasing amounts of biomedical information.

The National Institute of General Medical Sciences has awarded $15.4 million to the University of California, San Diego, to establish a center for the study of systems biology, a relatively new branch of science that maps interactions between regulatory molecules in order to understand how complex biological systems work.

The UC San Diego Center for Systems Biology will focus on interactions involved in cells’ responses to stress, said director Alexander Hoffmann, professor of chemistry and biochemistry in the Division of Physical Sciences.

Researchers at the new center will analyze interactions among all of the genes and proteins within a cell in response to potentially harmful changes in the environment, then test the functions of specific genetic “circuits” involved in the response by recreating them in isolation using synthesized genes.

Philip E. Bourne, a computational biologist and professor with the University of California, San Diego, is this year’s recipient of Microsoft’s Jim Gray eScience Award, for his contributions to data-intensive computing. “Phil's contributions to open access in bioinformatics and computational biology are legion, and are exactly the sort of groundbreaking accomplishments in data-intensive science that we celebrate with the Jim Gray Award,” said Tony Hey, corporate vice president of the External Research Division of Microsoft Research, in a corporate blog this week following the announcement. “In particular, Phil's role as the founding editor-in-chief of the open-access journal PLoS Computational Biology has significantly advanced open access in mathematical and computational biology.”

Shankar Subramaniam has been named a Distinguished Scientist at the San Diego Supercomputer Center (SDSC), to assist the Organized Research Unit of the University of California, San Diego, in identifying new opportunities and solutions in the area of bioinformatics.

A total of $375,000 has been awarded to the 2010-2011 Hellman Faculty Fellows at the University of California, San Diego. The funds awarded will support 30 faculty members in their scholarly work as they strive for tenure with the university, including Dr. Amy Kiger in cell and developmental biology.

Lucila Ohno-Machado, MD, PhD, FACMI and founding chief of the division of biomedical informatics at the University of California, San Diego has been named editor of the American Medical Informatics Association’s journal, JAMIA.

Two scientists from UC San Diego have been elected to the governing council of the National Academy of Sciences, the nation’s preeminent organization of scientists, which advises Congress and the U.S. government on matters of science and technology. They are former UC San Diego Chancellor and University of California President Robert C. Dynes, now a professor of physics at UCSD, and Susan S. Taylor, a professor in UCSD’s Department of Chemistry and Biochemistry and Department of Pharmacology, and a Howard Hughes Medical Institute Investigator.

Five professors at the University of California, San Diego have been named 2009 Fellows of the American Association for the Advancement of Science, the nation’s largest scientific organization. Don W. Cleveland, Steve A. Kay, Kimberly Prather, Michael G. Rosenfeld and Robert Schmidt were among 531 individuals this year selected by colleagues in their disciplines to be honored by the association for “efforts toward advancing science applications that are deemed scientifically or socially distinguished.”

As breakthrough discoveries in bioengineering become more crucial to fundamental global issues, including health, food production and water supplies, UC San Diego’s Jacobs School of Engineering’s top ranked bioengineering department continues to be on the cutting edge of this field. The Siebel Foundation has recognized the Jacob School’s pioneering efforts with a $2 million endowment to fund fellowships for some of its top bioengineering graduate students. The 2010 UC San Diego Siebel Scholars in bioengineering include Terrell Green, Amy Hsieh, Jennifer Singelyn, Julio Ng and Roy Lefkowitz.

Two scientists and a mathematician from the University of California, San Diego were named Fellows of the American Academy of Arts and Sciences on April 20. José Nelson Onuchic, professor of physics and co-director of the Center for Theoretical Biological Physics; Ruth Williams, professor of mathematics; and Martin Yanofsky, professor of biology and chair of the Section of Cell and Developmental Biology were recognized this year.

The American Academy of Arts & Sciences honors the country's leaders in scholarship, business, the arts and public affairs. New members will be formally welcomed into the Academy at an Induction Ceremony in Cambridge, Massachusetts, on October 10, 2009.

University of California, San Diego bioengineering professor Trey Ideker—a network and systems biology pioneer—has won the International Society for Computational Biology’s Overton Prize. The Overton prize is awarded each year to an early-to-mid-career scientist who has already made a significant contribution to the field of computational biology.

Bing Ren, Ph.D., associate professor of Cellular and Molecular Medicine at the University of California, San Diego School of Medicine and head of the Laboratory of Gene Regulation at the Ludwig Institute for Cancer Research, was recently selected as one of four grant recipients in the National Institutes of Health (NIH) Roadmap’s Epigenomics Program, an initiative developed to study stable genetic modifications that affect and alter the behavior of genes across the human genome.